The present invention concerns highly water soluble, stable, crystalline antiviral (including antiretroviral) salts of 2',3'-dideoxyinosine, 2',3'-dideoxy-2',3'-didehydrothymidine and 2',3'-dideoxy-2'-fluoroinosine, particularly sodium or potassium salts thereof.
Infectious viral diseases are recognized as an important medical problem. Progress against infectious viral disease requires the development of drugs with selective antiviral activity, while remaining benign to normal cell lines. A number of antiviral agents currently under study which seem to possess some selectivity are nucleoside analogs. In general, these compounds are structural analogs of the naturally occurring nucleosides. Structural modification in either the purine or pyrimidine base nucleus and/or the saccharide component results in a synthetically modified nucleoside derivative which, when incorporated into a viral nucleic acid forming process, acts to disrupt further synthesis of viral nucleic acid.
Effectiveness of these antiviral agents depends on selective conversion by viral enzymes, but not by host enzymes, to the corresponding nucleotide analog which is then converted to the triphosphate followed by incorporation into viral nucleic acid. A problem with this antiviral strategy has been the emergence of certain viral strains whose enzymes poorly promote phosphorylation of the nucleoside analogs. To circumvent this problem, intact nucleotide analogs appear to be potentially quite useful as antivirals for incorporation into viral nucleic acid.
PCT application WO 87/01284 to Mitsuya and Broder describes the use of 2',3'-dideoxyinosine ("ddI") for use against AIDS.
EP 0 273 277 to Lin and Prusoff discloses the use of 2',3'-dideoxy-2',3'-didehydrothymidine ("d4T") in treating patients infected with a retrovirus.
Erik De Clercq, "Potential Drugs for the Treatment of AIDS", Journal of Antimicrobial Chemotherapy, 23, Suppl. A, 35-46, (1989), describes the use of dideoxynucleoside analogues to inhibit the infectivity and cytopathic effect of human immunodeficiency virus ("HIV")
EP 0 287 313 discloses 2',3'-dideoxy-2'-fluoroinosine ("F-ddI") and its activity against HIV.